More than 80% of women experience vasomotor symptoms (VMS; hot flashes and night sweats) during the menopausal transition. The use of hormone therapy, the standard treatment for VMS, decreased by 75% after publication of the findings from the Women's Health Initiative. The only FDA-approved nonhormonal treatment for VMS is paroxetine, a low-dose antidepressant that showed significant but modest efficacy in randomized trials. In the past decade, our understanding of the efficacy of nonhormonal therapies on VMS has increased considerably based on findings from randomized clinical trials. Unfortunately, the results from these trials show no-to-minimal efficacy, and two nonhormonal VMS medications recently failed to win FDA approval. Women therefore have very few nonhormonal treatment options for VMS. To address the continuing need for development of new nonhormonal therapies for VMS, we propose a multidisciplinary, 2-day conference, The Science of Thermoregulation and Vasomotor Symptoms: Possible New Targets for Treatment. The conference will convene a diverse group of 20 to 25 basic and clinical researchers as well as clinicians to discuss normal and aberrant thermoregulation, the neurophysiology of VMS, and new potential treatment targets. The aim of the conference is to facilitate synthesis and exchange of new data by promoting scientific exchange among experts who do not typically interact scientifically but whose work informs the others. In recent years, scientific understanding of the mechanisms involved in VMS has evolved considerably based on findings from basic science, physiology, neuroimaging, and studies of skin dynamics. The specific aims are to 1) describe current understanding of the physiology and neuropharmacology of thermoregulation and VMS; 2) describe current understanding of nonhormonal treatments for VMS; 3) review existing evidence from studies linking VMS to adverse health outcomes in women, including quality of life, cardiovascular outcomes, and cognitive function; 4) integrate new and emerging data from multiple areas of inquiry into an initial conceptual framework to better understand the causal pathway of VMS and potential avenues for new drug development. The Day 1 public symposium, open to 80 participants, will feature oral and poster presentations of recent scientific advances in thermoregulation and VMS and discussion of the implications of this new evidence for the development of nonhormonal VMS treatments. On Day 2, facilitated working groups will discuss and respond to targeted questions regarding research priorities. We offer four travel awards for new investigators. The meeting will be sponsored by The North American Menopause Society (NAMS) and will take place October 14-15, 2014, just before the 25th NAMS Annual Meeting in Washington, DC. The symposium recommendations will be presented in a special session at the NAMS meeting. A Program Planning Committee will prepare a conference summary for oral presentation at the NAMS Annual Meeting, an executive summary of the recommendations for publication in the official NAMS journal, Menopause, and a lay version to be published on the NAMS website.